normal embryonic development
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Author(s):  
Mays Abuhantash ◽  
Emma M. Collins ◽  
Alexander Thompson

Hematopoiesis, the process of blood formation, is controlled by a complex developmental program that involves intrinsic and extrinsic regulators. Blood formation is critical to normal embryonic development and during embryogenesis distinct waves of hematopoiesis have been defined that represent the emergence of hematopoietic stem or progenitor cells. The Class I family of homeobox (HOX) genes are also critical for normal embryonic development, whereby mutations are associated with malformations and deformity. Recently, members of the HOXA cluster (comprising 11 genes and non-coding RNA elements) have been associated with the emergence and maintenance of long-term repopulating HSCs. Previous studies identified a gradient of HOXA expression from high in HSCs to low in circulating peripheral cells, indicating their importance in maintaining blood cell numbers and differentiation state. Indeed, dysregulation of HOXA genes either directly or by genetic lesions of upstream regulators correlates with a malignant phenotype. This review discusses the role of the HOXA cluster in both HSC emergence and blood cancer formation highlighting the need for further research to identify specific roles of these master regulators in normal and malignant hematopoiesis.


2021 ◽  
Author(s):  
Rongjia Zhang ◽  
Yuhuan Liu

Male pregnancy is a unique phenomenon in syngnathidae which refers to the incubation of embryos or fetuses by males. However, whether male mammalian animals have the potential to conceive and maintain pregnancy remains unclear. Here, we constructed a rat model of male pregnancy by a four-step strategy: a heterosexual parabiotic pair was firstly produced by surgically joining a castrated male rat and a female rat. Uterus transplantation (UTx) was then performed on the male parabiont 8 weeks later. After recovery, blastocyst-stage embryos were transplanted to the grafted uterus of male parabiont and the native uterus of female parabiont. Caesarean section was performed at embryonic day (ED) 21.5. The success rate of modeling was only 3.68%, but 10 pups could still be delivered from male parabionts and developed. Our experiment reveals the possibility of normal embryonic development in male mammalian animals, and it may have a profound impact on reproductive biology.


Author(s):  
Hao Zhang ◽  
Ya Bao ◽  
Chenglong Liu ◽  
Jianqi Li ◽  
Di Zhu ◽  
...  

Wnt/β-catenin signaling is crucial both in normal embryonic development and throughout the life of an organism. Moreover, aberrant Wnt signaling has been associated with various diseases, especially cancer and fibrosis. Recent research suggests that direct targeting of the β-catenin/BCL9 protein–protein interaction (PPI) is a promising strategy to block the Wnt pathway. Progress in understanding the cocrystalline complex and mechanism of action of the β-catenin/BCL9 interaction facilitates the discovery process of its inhibitors, but only a few inhibitors have been reported. In this review, the discovery and development of β-catenin/BCL9 PPI inhibitors in the areas of drug design, structure–activity relationships and biological and biochemical properties are summarized. In addition, perspectives for the future development of β-catenin/BCL9 PPI inhibitors are explored.


2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Lin Yang ◽  
Zihao Su ◽  
Ziwu Wang ◽  
Zhenmeiyu Li ◽  
Zicong Shang ◽  
...  

AbstractThe striatum is structurally highly diverse, and its organ functionality critically depends on normal embryonic development. Although several studies have been conducted on the gene functional changes that occur during striatal development, a system-wide analysis of the underlying molecular changes is lacking. Here, we present a comprehensive transcriptome profile that allows us to explore the trajectory of striatal development and identify the correlation between the striatal development and Huntington’s disease (HD). Furthermore, we applied an integrative transcriptomic profiling approach based on machine learning to systematically map a global landscape of 277 transcription factor (TF) networks. Most of these TF networks are linked to biological processes, and some unannotated genes provide information about the corresponding mechanisms. For example, we found that the Meis2 and Six3 were crucial for the survival of striatal neurons, which were verified using conditional knockout (CKO) mice. Finally, we used RNA-Seq to speculate their downstream targets.


Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 263
Author(s):  
Alessia Indrieri ◽  
Brunella Franco

Mitochondrial disorders, although heterogeneous, are traditionally described as conditions characterized by encephalomyopathy, hypotonia, and progressive postnatal organ failure. Here, we provide a systematic review of Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA), a rare, unconventional mitochondrial disorder which presents as a developmental disease; its main clinical features include microphthalmia with different degrees of severity, linear skin lesions, and central nervous system malformations. The molecular basis of this disorder has been elusive for several years. Mutations were eventually identified in three X-linked genes, i.e., HCCS, COX7B, and NDUFB11, which are all endowed with defined roles in the mitochondrial respiratory chain. A peculiar feature of this condition is its inheritance pattern: X-linked dominant male-lethal. Only female or XX male individuals can be observed, implying that nullisomy for these genes is incompatible with normal embryonic development in mammals. All three genes undergo X-inactivation that, according to our hypothesis, may contribute to the extreme variable expressivity observed in this condition. We propose that mitochondrial dysfunction should be considered as an underlying cause in developmental disorders. Moreover, LSDMCA should be taken into consideration by clinicians when dealing with patients with microphthalmia with or without associated skin phenotypes.


Author(s):  
Alessia Indrieri ◽  
Brunella Franco

Mitochondrial disorders, although heterogeneous, are traditionally described as conditions characterized by encephalomyopathy, hypotonia and progressive postnatal organ failure. Here we provide a systematic review of Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA), a rare unconventional mitochondrial disorder which presents as a developmental disease; its main clinical features include microphthalmia with different degrees of severity, linear skin lesions, and central nervous system malformations. The molecular basis of this disorder has been elusive for several years. Mutations were eventually identified in three X-linked genes, i.e., HCCS, COX7B, and NDUFB11, which are all endowed with defined roles in the mitochondrial respiratory chain. A peculiar feature of this condition is its inheritance pattern: X-linked dominant male-lethal. Only female or XX male individuals can be observed, implying that nullisomy for these transcripts is incompatible with normal embryonic development in mammals. All three genes undergo X-inactivation that, according to our hypothesis, may contribute to the extreme variable expressivity observed in this condition. We propose that mitochondrial dysfunction should be considered as an underlying cause in developmental disorders. Moreover, LSDMCA should be taken into consideration by clinicians when dealing with patients with microphthalmia with or without associated skin phenotypes.


2020 ◽  
Vol 17 (6) ◽  
pp. 815-823
Author(s):  
Ju-Young Lee ◽  
Faiz Ur Rahman ◽  
Eun-Kyeung Kim ◽  
Sang-Mi Cho ◽  
Hae-rim Kim ◽  
...  

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Joyce C. K. Man ◽  
Rajiv A. Mohan ◽  
Malou van den Boogaard ◽  
Catharina R. E. Hilvering ◽  
Catherine Jenkins ◽  
...  

Abstract Mutations and variations in and around SCN5A, encoding the major cardiac sodium channel, influence impulse conduction and are associated with a broad spectrum of arrhythmia disorders. Here, we identify an evolutionary conserved regulatory cluster with super enhancer characteristics downstream of SCN5A, which drives localized cardiac expression and contains conduction velocity-associated variants. We use genome editing to create a series of deletions in the mouse genome and show that the enhancer cluster controls the conformation of a >0.5 Mb genomic region harboring multiple interacting gene promoters and enhancers. We find that this cluster and its individual components are selectively required for cardiac Scn5a expression, normal cardiac conduction and normal embryonic development. Our studies reveal physiological roles of an enhancer cluster in the SCN5A-SCN10A locus, show that it controls the chromatin architecture of the locus and Scn5a expression, and suggest that genetic variants affecting its activity may influence cardiac function.


2019 ◽  
Author(s):  
Kaili K. Li ◽  
Dongsheng Han ◽  
Fang Chen ◽  
Ruihao Li ◽  
Bing-Rui Zhou ◽  
...  

SummaryHistone variants carry specific functions in addition to those fulfilled by their canonical counterparts. Variants of the linker Histone H1 are prevalent in vertebrates and based on the pattern of their expression, many are presumed to function during germline and the earliest zygotic stages of development. While the existence of multiple H1 variants has hampered their study in vertebrates, a single variant, BigH1, was identified in Drosophila, promising to accelerate our understanding of the biological functions of H1 and H1 variants. Here we uncovered evidence for a compensatory activity that loads maternal H1 onto BigH1-devoid chromatin. Remarkably, this H1-based chromatin state is fully functional in supporting normal embryonic development, suggesting that H1 carries the essential function of the BigH1 molecule under the same developmental context. In addition, we discovered that this compensatory replacement of BigH1 with H1 might be limited to rapidly cycling cells in early embryos.


2019 ◽  
Vol 50 (1) ◽  
pp. 7-8 ◽  
Author(s):  
Colin C. Conine ◽  
Fengyun Sun ◽  
Lina Song ◽  
Jaime A. Rivera-Pérez ◽  
Oliver J. Rando

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